DOCSLIB.ORG

Pancreatic Glucagonoma Metastasising to the Right Ovary Five Years After Initial Surgery: a Case Report

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Pancreatic Glucagonoma Metastasising to the Right Ovary Five Years After Initial Surgery: a Case Report JOP. J Pancreas (Online) 2013 Sep 10; 14(5):510-514. CASE REPORT Pancreatic Glucagonoma Metastasising to the Right Ovary Five Years after Initial Surgery: A Case Report David Graham Watt 1, Sanjay Pandanaboyana 4, Charles Simon Herrington 2, Iain S Tait 3 1General Surgery, 2Department of Pathology, and 3Hepatobiliary and Pancreatic Surgery, Ninewells Hospital and Medical School. Dundee, Scotland, United Kingdom. 4Hepatobiliary and Transplant Surgery, St James University Hospital. Leeds, West Yorkshire, United Kingdom ABSTRACT Context Glucagonomas of the pancreas are neuroendocrine tumours (NETs) that arise from well-differentiated neuroendocrine cells within the pancreatic islets. They are considered to be aggressive NETs and often have metastases at initial presentation. In contrast localised glucagonoma without metastatic spread may have prolonged disease free survival with radical resectional surgery. Case report The authors present a case of a glucagonoma that initially presented with classical necrolytic migratory erythema and a large solitary mass in the body and tail of the pancreas that was surgically resected. Five years after surgery the patient presented with increased serum glucagon levels and a mass in the right ovary. Pathology of the resected ovary after oophorectomy identified this as an isolated metastatic glucagonoma. Conclusion Glucagonoma is a rare pancreatic NET that has significant malignant potential. This is the first case of a pancreatic glucagonoma metastasising to the ovary 5 years after radical distal pancreatosplenectomy. INTRODUCTION [3] and has an incidence of 1 in 20,000,000 per year [4]. Pancreatic neuroendocrine tumours (NETs) are rare tumours of the pancreatic islet cells. NETs arise The authors present a case of pancreatic from mature endocrine cells in the pancreas or glucagonoma localised to the body and tail of the multi-potent stem cells and express chromogranin pancreas that was resected in 2007 by laparoscopic A, synaptophysin and/or neuron-specific enolase. distal pancreatosplenectomy. In February 2012 (5 NETs may also secrete neuropeptides that may years later) the patient presented with raised cause clinical symptoms or syndromes, such as glucagon levels and a mass in the pelvis on cross- Zollinger-Ellison syndrome (gastrinoma) or sectional imaging. At laparoscopy a large solitary necrolytic migratory erythema (glucagonoma). right ovarian mass was identified and resected. Pathological examination of the ovary identified this There are various types of NETs including as metastatic NET consistent with glucagonoma. insulinomas, gastrinomas, VIPomas, carcinoid This is the first reported case of isolated metastatic tumours and glucagonomas [1]. Surgery is the only glucagonoma in the ovary, five years after resection curative treatment for those tumours that are of a primary pancreatic glucagonoma. localised at presentation [2]. A glucagonoma is derived from the alpha cells of the pancreas. As the CASE REPORT name suggests, these cells are usually responsible A 62-year-old lady presented to the dermatology for the production of glucagon in the body. clinic with a 36-month history of dermatosis Glucagonoma was first described by Becker in 1942 affecting the lower legs, axillae, groins and sub- mammary regions (Figures 1 and 2). The rash was Received June 1 st , 2013 – Accepted August 2 nd , 2013 intermittent in nature, non-pruritic, associated with Key words Glucagonoma; Neoplasm Metastasis; Neuro- hair thinning, and had not responded to topical endocrine Tumors; Ovarian Neoplasms; Pancreatic Neoplasms treatments. Skin patch testing was negative and Abbreviations NET: neuroendocrine tumour therefore skin biopsies were taken. These biopsies Correspondence Iain S Tait Department of General Surgery; Ninewells Hospital and showed necrolytic migratory erythema. Blood tests Medical School; Dundee DD1 9SY; Scotland; United Kingdom were ordered to include minerals and electrolytes, Phone: +44-1382.660.111; Fax: +44-1382.496.361 chromogranin A and glucagon levels. Zinc levels E-mail: [email protected] were found to be low, N-terminal glucagon raised at JOP. Journal of the Pancreas - http://www.serena.unina.it/index.php/jop - Vol. 14 No. 5 – September 2013. [ISSN 1590-8577] 510 JOP. J Pancreas (Online) 2013 Sep 10; 14(5):510-514. Figure 1. Dermatosis affecting the axilla that was shown to be Figure 2. Dermatosis affecting the lower legs that was shown to necrolytic migratory erythema following skin biopsy. be necrolytic migratory erythema following skin biopsy. 965 ng/L (reference range: 0-250 ng/L) and c- Five years after laparoscopic distal pancreato- terminal glucagon raised at 580 ng/L (reference splenectomy, surveillance glucagon levels showed a range: 0-150 ng/L). The biochemical diagnosis of a slight elevation whilst the patient remained pancreatic glucagonoma was confirmed and cross- otherwise well and asymptomatic. CT scanning sectional imaging demonstrated a 5 cm mass lesion showed a suspicious lesion in the distal small bowel, in the body and tail of the pancreas with no deep in the pelvis, with mucosal thickening and evidence of nodal disease or other metastatic hyper-enhancement. This was thought to be a spread (Figure 3). primary neuroendocrine tumour of the small bowel (Figure 4), as this would be regarded as an unusual The patient underwent a laparoscopic radical site for recurrence of a primary pancreatic NET. antegrade pancreatosplenectomy in February 2007 and the patient made an excellent post-operative recovery. Pathology confirmed this to be a neuroendocrine tumour with evidence of glucagon production, staged as pT2, pN0, pMx. Histology demonstrated a uniform appearance with islands and trabeculae of cells with pink cytoplasm and open nuclei. These features were in keeping with a glucagonoma that was completely excised (R0). A baseline early post-operative octreotide scan at 3 months showed no evidence of occult metastatic disease. Genetics showed no evidence of mutation in the MEN 1 gene and, following surgery the necrolytic migratory erythema rash rapidly resolved. The patient was placed on a surveillance programme of 6 monthly monitoring of serum glucagon levels and annual CT scan of chest and Figure 3. Cross sectional CT scanning showing a mass in the tail abdomen. of the pancreas (red arrow). JOP. Journal of the Pancreas - http://www.serena.unina.it/index.php/jop - Vol. 14 No. 5 – September 2013. [ISSN 1590-8577] 511 JOP. J Pancreas (Online) 2013 Sep 10; 14(5):510-514. the right ovary looked markedly abnormal and contained a large tumour, with no evidence of peritoneal disease, and no evidence of liver metastases. A laparoscopic right oophorectomy was performed and the patient made a good post- operative recovery and was discharged home. Macroscopically, the ovary was enlarged, measuring 50x40x55 mm, and weighed 55 g. It had a nodular appearance with an intact outer capsule. On sectioning, the ovary contained a multilocular cystic lesion, the largest cystic space measuring 20 mm in diameter. The non-cystic areas of the ovary had a yellow cut surface. Microscopic analysis Figure 4. Cross sectional CT scanning demonstrating an demonstrated tumour cells with monomorphic abnormality in the pelvis, thought to be dilated terminal ileum with mucosal thickening and hyper-enhancement (red arrow). nuclei and pale pink cytoplasm arranged predominantly in glandular and trabecular structures (Figure 5ab). Immunohistochemistry As there was uncertainty of the nature of the mass showed diffuse expression by tumour cells of lesion in the distal small bowel, which was cytokeratin 18 and synaptophysin (Figure 5c), with considered to be a most unusual site for focal expression of chromogranin and cytokeratin glucagonoma recurrence, a laparoscopy was 19, and cytoplasmic positivity for glucagon (Figure performed. At laparoscopy, the entire small bowel 5d). Overall the appearances indicated a was examined and no lesion identified. However, neuroendocrine tumour, and were compatible with Figure 5. Photo microscopy from the resected ovarian specimen. a. This panel shows a low power view stained with haematoxylin and eosin (H&E; total magnification x40). The tumour is shown with the black arrow and ovarian cortex with yellow arrow. b. This panel is a high power view of the tumour cells, confirming the neuroendocrine appearance (H&E; total magnification x200). c. Section stained with synaptophysin which is a marker of neuroendocrine differentiation (total magnification x200). d. Section of tumour stained with glucagon, in keeping with metastatic glucagonoma (total magnification x200). JOP. Journal of the Pancreas - http://www.serena.unina.it/index.php/jop - Vol. 14 No. 5 – September 2013. [ISSN 1590-8577] 512 JOP. J Pancreas (Online) 2013 Sep 10; 14(5):510-514. an ovarian metastasis from the original [11]. Our case further demonstrates that glucagonoma. The patient remains well at 16 laparoscopic surgery is safe and effective for months follow-up after oophorectomy, and with no treating neuroendocrine tumours of the pancreas, evidence of any further metastatic disease (now and curative resection can be achieved with good more than 6 years after laparoscopic resection of post-operative outcomes. the primary glucagonoma). Pancreatic NETs usually spread to the liver, lungs DISCUSSION and peritoneum [1, 2, 3, 4, 5], and there are currently no reported cases of primary The first pancreatic “hormone-producing tumours” neuroendocrine tumours of the pancreas were described by Wilder et al. in 1927,
Load more

Recommended publications
  • Effects of Streptozotocin-Induced Diabetes on the Pineal Gland in the Domestic Pig
    International Journal of Molecular Sciences Article Effects of Streptozotocin-Induced Diabetes on the Pineal Gland in the Domestic Pig Bogdan Lewczuk 1,* , Magdalena Prusik 1 , Natalia Ziółkowska 1, Michał D ˛abrowski 2, Kamila Martniuk 1, Maria Hanuszewska 1 and Łukasz Zielonka 2 1 Department of Histology and Embryology, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, Oczapowskiego 13, 10-719 Olsztyn, Poland; [email protected] (M.P.); [email protected] (N.Z.); [email protected] (K.M.); [email protected] (M.H.) 2 Department of Veterinary Prevention and Feed Hygiene, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, Oczapowskiego 13, 10-719 Olsztyn, Poland; [email protected] (M.D.); [email protected] (Ł.Z.) * Correspondence: [email protected]; Tel.: +48-89-523-39-49; Fax: +48-89-523-34-40 Received: 15 July 2018; Accepted: 5 October 2018; Published: 9 October 2018 Abstract: Several observations from experiments in rodents and human patients suggest that diabetes affects pineal gland function, including melatonin secretion; however, the accumulated data are not consistent. The aim of the present study was to determine the effects of streptozotocin-induced diabetes on the pineal gland in the domestic pig, a species widely used as a model in various biomedical studies. The study was performed on 10 juvenile pigs, which were divided into two groups: control and diabetic. Diabetes was evoked by administration of streptozotocin (150 mg/kg of body weight). After six weeks, the animals were euthanized between 12.00 and 14.00, and the pineal glands were removed and divided into two equal parts, which were used for biochemical analyses and for preparation of explants for the superfusion culture.
    [Show full text]
  • Endocrine Tumors of the Pancreas
    Friday, November 4, 2005 8:30 - 10:30 a. m. Pancreatic Tumors, Session 2 Chairman: R. Jensen, Bethesda, MD, USA 9:00 - 9:30 a. m. Working Group Session Pathology and Genetics Group leaders: J.–Y. Scoazec, Lyon, France Questions to be answered: 12 Medicine and Clinical Pathology Group leader: K. Öberg, Uppsala, Sweden Questions to be answered: 17 Surgery Group leader: B. Niederle, Vienna, Austria Questions to be answered: 11 Imaging Group leaders: S. Pauwels, Brussels, Belgium; D.J. Kwekkeboom, Rotterdam, The Netherlands Questions to be answered: 4 Color Codes Pathology and Genetics Medicine and Clinical Pathology Surgery Imaging ENETS Guidelines Neuroendocrinology 2004;80:394–424 Endocrine Tumors of the Pancreas - gastrinoma Epidemiology The incidence of clinically detected tumours has been reported to be 4-12 per million inhabitants, which is much lower than what is reported from autopsy series (about 1%) (5,13). Clinicopathological staging (12, 14, 15) Well-differentiated tumours are the large majority of which the two largest fractions are insulinomas (about 40% of cases) and non-functioning tumours (30-35%). When confined to the pancreas, non-angioinvasive, <2 cm in size, with <2 mitoses per 10 high power field (HPF) and <2% Ki-67 proliferation index are classified as of benign behaviour (WHO group 1) and, with the notable exception of insulinomas, are non-functioning. Tumours confined to the pancreas but > 2 cm in size, with angioinvasion and /or perineural space invasion, or >2mitoses >2cm in size, >2 mitoses per 20 HPF or >2% Ki-67 proliferation index, either non-functioning or functioning (gastrinoma, insulinoma, glucagonoma, somastatinoma or with ectopic syndromes, such as Cushing’s syndrome (ectopic ACTH syndrome), hypercaliemia (PTHrpoma) or acromegaly (GHRHoma)) still belong to the (WHO group 1) but are classified as tumours with uncertain behaviour.
    [Show full text]
  • C O N F E R E N C E 7 18 October 2017
    Joint Pathology Center Veterinary Pathology Services WEDNESDAY SLIDE CONFERENCE 2017-2018 C o n f e r e n c e 7 18 October 2017 CASE I: F1753191 (JPC 4101076). veterinarian revealed a regenerative anemia, stress leukogram and hypoproteinemia Signalment: 9-year-old, female intact, Rock characterized by hypoalbuminemia and the Alpine goat, Capra aegagrus hircus, goat was treated with ivermectin. caprine. Bloodwork at CSU revealed hyperglycemia and elevated creatinine, creatine kinase and History: A 9-year-old, female intact Rock aspartate aminotransferase levels. A fecal Alpine goat presented to Colorado State floatation revealed heavy loads of coccidia, University Veterinary Teaching Hospital strongyles and Trichuris spp. During a nine two months prior to necropsy with a three- day hospitalization, the doe was treated with day history of hyporexia and lethargy which intravenous fluids, kaopectate, thiamine, had progressed to lateral recumbency and fenbendazole, sulfadimethoxine, oxy- complete anorexia. The referring tetracycline and multiple blood transfusions. veterinarian had previously diagnosed the After significant improvement of her clinical doe with louse infestation, endoparasites and signs and bloodwork, including partial a heart murmur. Bloodwork by the referring resolution of the dermatitis, the doe was Haired skin goat. The skin was dry, alopecia, and covered with hyperkeratotic crusts and ulcers. (Photo courtesy of: Colorado State University, Microbiology, Immunology, and Pathology Department, College of Veterinary Medicine and Biomedical Sciences, http://csucvmbs.colostate.edu/academics/mip/Pages/default.aspx) 1 discharged. exfoliating epithelial crusts which were often tangled within scant remaining hairs. Two months later, the goat presented with a This lesion most severely affected the skin one month history of progressive scaling and over the epaxials, the ventral abdomen and ulceration over the withers, dew claws, and teats, coronary bands and dew claws.
    [Show full text]
  • Endocrine Cell Type Sorting and Mature Architecture in the Islets Of
    www.nature.com/scientificreports OPEN Endocrine cell type sorting and mature architecture in the islets of Langerhans require expression of Received: 16 April 2018 Accepted: 4 July 2018 Roundabout receptors in β cells Published: xx xx xxxx Melissa T. Adams, Jennifer M. Gilbert, Jesus Hinojosa Paiz, Faith M. Bowman & Barak Blum Pancreatic islets of Langerhans display characteristic spatial architecture of their endocrine cell types. This architecture is critical for cell-cell communication and coordinated hormone secretion. Islet architecture is disrupted in type-2 diabetes. Moreover, the generation of architecturally correct islets in vitro remains a challenge in regenerative approaches to type-1 diabetes. Although the characteristic islet architecture is well documented, the mechanisms controlling its formation remain obscure. Here, we report that correct endocrine cell type sorting and the formation of mature islet architecture require the expression of Roundabout (Robo) receptors in β cells. Mice with whole-body deletion of Robo1 and conditional deletion of Robo2 either in all endocrine cells or selectively in β cells show complete loss of endocrine cell type sorting, highlighting the importance of β cells as the primary organizer of islet architecture. Conditional deletion of Robo in mature β cells subsequent to islet formation results in a similar phenotype. Finally, we provide evidence to suggest that the loss of islet architecture in Robo KO mice is not due to β cell transdiferentiation, cell death or loss of β cell diferentiation or maturation. Te islets of Langerhans display typical, species-specifc architecture, with distinct spatial organization of their various endocrine cell types1–5. In the mouse, the core of the islet is composed mostly of insulin-secreting β cells, while glucagon-secreting α cells, somatostatin-secreting δ cells and pancreatic polypeptide-secreting PP cells are located at the islet periphery3.
    [Show full text]
  • The Role of Thyroid Hormone
    Central Journal of Endocrinology, Diabetes & Obesity Mini Review Special Issue on Role of Thyroid Hormone Pancreatic and Islet Develop- in Metabolic Homeostasis ment and Function: The Role of *Corresponding authors Teresa L Mastracci, Department of Pediatrics, Indiana University School of Medicine, Herman B Wells Center for Thyroid Hormone Pediatric Research, 635 Barnhill Dr, MS2031, Indianapolis, IN, USA 46202, Tel: 317-278-8940; Fax: 317-274-4107; Teresa L Mastracci1,5* and Carmella Evans-Molina2,3,4,5* Email: 1Department of Pediatrics, Indiana University School of Medicine, USA Carmella Evans-Molina, Department of Medicine, 2Department of Medicine, Indiana University School of Medicine, USA Cellular and Integrative Physiology, Biochemistry and 3Department of Cellular and Integrative Physiology, Indiana University School of Molecular Biology, Herman B Wells Center for Pediatric Medicine, USA Research, Indiana University School of Medicine, 4Department of Biochemistry and Molecular Biology, Indiana University School of Indiana University School of Medicine, 635 Barnhill Dr., Medicine, USA MS2031, Indianapolis, IN, USA 46202, Tel: 317-278-3177; 5Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Fax: 317-274-4107; Email: USA Submitted: 12 June 2014 Accepted: 17 July 2014 Published: 19 July 2014 Abstract ISSN: 2333-6692 A gradually expanding body of literature suggests that Thyroid Hormone (TH) Copyright and Thyroid Hormone Receptors (TRs) play a contributing role in pancreatic and islet © 2014 Mastracci et al. cell development, maturation, and function. Studies using a variety of model systems capable of exploiting species-specific developmental paradigms have revealed the OPEN ACCESS contribution of TH to cellular differentiation, lineage decisions, and endocrine cell specification.
    [Show full text]
  • Production of the a Subunit of Guanine Nucleotide-Binding Protein GO by Neuroendocrine Tumors1
    [CANCER RESEARCH 47, 5800-5805, November 1, 1987] Production of the a Subunit of Guanine Nucleotide-binding Protein GO by Neuroendocrine Tumors1 Kanefusa Kato,2 Tomiko Asano, Nobuko Kamiya, Hajime Haimoto, Syun Hosoda, Akio Nagasaka, Yutaka Ariyoshi, and Yukio Ishiguro Department of Biochemistry ¡K.K„T.A., N. K.], Institute for Developmental Research, Aichi Prefectural Colony, Kasugai, Aichi 480-03; Laboratory of Pathology ¡H.H., S. H.] and Department of Internal Medicine [Y, A.], Aichi Cancer Center, Chikusa-ku, Nagoya 464; Department of Internal Medicine [A. N.J. Fujita-Gakuen Health University, School of Medicine, Toyoake, Aichi 470-11; and Department of Surgery [Y. IJ, Nagoya University School of Medicine, Showa-ku, Nagoya 466, Japan ABSTRACT is localized exclusively in the nervous tissues and some endo crine cells in pancreas, pituitary, thyroid, and adrenal,4 which We have found that neuroendocrine tumors (including neuroblastoma, belong to a family designated as APUD (amine precursor ganglioneuroma, gut carcinoid, pheochromocytoma, medullary thyroid uptake and decarboxylation) or diffuse neuroendocrine system carcinoma, insulinoma, glucagonoma, prolactinoma, carotid body tumor, (10). We describe here the presence of G0«in tumors derived and small cell lung carcinoma) produce considerable amounts (about 1000-80,000 ng/g tissue) of the a subunit of guanine nucleotide-binding from the above mentioned neuroendocrine cells and in sera of protein, G0 (Goa), whereas nonneuroendocrine tumors contain less than patients with neuroblastoma, and evaluate G0a for the appli 300 ng of Goa/g tissue. Goat in the neuroendocrine tumors was present cation to clinical and immunohistochemical diagnosis. both in the soluble fraction, and cholate-extractable membrane-bound fraction of tissues.
    [Show full text]
  • GLP-1 Effects on Islets: Hormonal, Neuronal, Or Paracrine?
    DIABETES PATHOPHYSIOLOGY GLP-1 Effects on Islets: Hormonal, Neuronal, or Paracrine? 1 MARC Y. DONATH, MD control of glycemia through the activation 2 RÉMY BURCELIN, PHD of the gut brain axis. Furthermore, the di- rect administration of the DPP-4 inhibitor into the rat portal vein significantly in- creased portal (but not peripheral) GLP-1 ccording to the classical incretin con- (5) within minutes from the absorption and insulin levels and decreased glucose Acept, glucagon-like peptide (GLP)-1 of glucose and lipids. The final aim of concentrations (14). However, despite the is viewed as a hormone produced this axis is to anticipate the breakthrough large amount of experimental evidence de- in the intestinal L cells and acting via of the nutrients into the blood and their scribed above showing the important role the circulation on satiety in the brain, better handling. Indeed, GLP-1 secreted of GLP-1 on the gut-to-brain axis, a recent gut motility, and insulin and glucagon from L cells can influence brain neuronal observation in mice suggests that the circu- secretion in the pancreatic islet. How- activities via an alternative neural path- lating GLP-1 could also directly access the ever, in contrast to typical hormones, way initiated by sensors in the hepatic brain and the b-cells and induce insulin plasma levels of GLP-1 are relatively low portal region (6–8). Thereby, the vagus secretion (15). Transgenic mice that ex- with a very short half-life. Furthermore, nerve transmits the metabolic infor- pressed the human GLP-1 receptor in islets GLP-1 is rapidly inactivated by dipep- mation to the nucleus tractus solitarii and in pancreatic ductal cells within the tidyl peptidase-4 (DPP-4) in the vicinity in the brain stem, which relays the glu- background of the GLP-1 receptor knock- of L cells within ,1 min from the secre- cose signal to hypothalamic nuclei (9).
    [Show full text]
  • Nomina Histologica Veterinaria, First Edition
    NOMINA HISTOLOGICA VETERINARIA Submitted by the International Committee on Veterinary Histological Nomenclature (ICVHN) to the World Association of Veterinary Anatomists Published on the website of the World Association of Veterinary Anatomists www.wava-amav.org 2017 CONTENTS Introduction i Principles of term construction in N.H.V. iii Cytologia – Cytology 1 Textus epithelialis – Epithelial tissue 10 Textus connectivus – Connective tissue 13 Sanguis et Lympha – Blood and Lymph 17 Textus muscularis – Muscle tissue 19 Textus nervosus – Nerve tissue 20 Splanchnologia – Viscera 23 Systema digestorium – Digestive system 24 Systema respiratorium – Respiratory system 32 Systema urinarium – Urinary system 35 Organa genitalia masculina – Male genital system 38 Organa genitalia feminina – Female genital system 42 Systema endocrinum – Endocrine system 45 Systema cardiovasculare et lymphaticum [Angiologia] – Cardiovascular and lymphatic system 47 Systema nervosum – Nervous system 52 Receptores sensorii et Organa sensuum – Sensory receptors and Sense organs 58 Integumentum – Integument 64 INTRODUCTION The preparations leading to the publication of the present first edition of the Nomina Histologica Veterinaria has a long history spanning more than 50 years. Under the auspices of the World Association of Veterinary Anatomists (W.A.V.A.), the International Committee on Veterinary Anatomical Nomenclature (I.C.V.A.N.) appointed in Giessen, 1965, a Subcommittee on Histology and Embryology which started a working relation with the Subcommittee on Histology of the former International Anatomical Nomenclature Committee. In Mexico City, 1971, this Subcommittee presented a document entitled Nomina Histologica Veterinaria: A Working Draft as a basis for the continued work of the newly-appointed Subcommittee on Histological Nomenclature. This resulted in the editing of the Nomina Histologica Veterinaria: A Working Draft II (Toulouse, 1974), followed by preparations for publication of a Nomina Histologica Veterinaria.
    [Show full text]
  • Why Pancreatic Islets Should Be Regarded and Regulated Like Organs
    CellR4 2021; 9: e3083 Why pancreatic islets should be regarded and regulated like organs G. C. Weir, S. Bonner-Weir Section on Islet Cell and Regenerative Biology, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA Corresponding Author: Gordon C. Weir, MD; e-mail: [email protected] Keywords: Autologous transplantation, Islet transplanta- islets transplants, processed exactly in the same way, tion, Pancreatic alpha cells, Pancreatic beta cells, Pancreatic are exempted from these drugs regulations in the islets. US. Alloislets are exempt from drug regulation, and safely and effectively offered as a standard-of-care ABSTRACT treatment option in a number of developed nations, There are strong reasons to say that pancreatic with the notable exception of the US. islets are organs before they are isolated and Some of the basis for distinguishing between that they should be considered to be organs once allogenic islets and other organ/vascularized com- transplanted. Thus, taking into account how posite tissues lies in taking the position that alloge- much we have learned about the structure and neic islets are not to be vascularized organs, which function of islet micro-organs, it seems highly led to the plan to regulate them as drugs, which is illogical to on one hand consider autologous how cellular transplants are regulated. islets be regulated as organ transplants and al- Although there are many complexities, there loislets to be regulated with the very restrictive is the simple question of whether islets are organs. rules used for cell transplantation. It is partic- The answer for many is clearly yes, and that would ularly problematic that this policy has led to pertain to both autologous islets and alloislets.
    [Show full text]
  • Rising Incidence of Neuroendocrine Tumors
    Rising Incidence of Neuroendocrine Tumors Dasari V, Yao J, et al. JAMA Oncology 2017 S L I D E 1 Overview Pancreatic Neuroendocrine Tumors • Tumors which arise from endocrine cells of the pancreas • 5.6 cases per million – 3% of pancreatic tumors • Median age at diagnosis 60 years • More indolent course compared to adenocarcinoma – 10-year overall survival 40% • Usually sporadic but can be associated with hereditary syndromes – Core genetic pathways altered in sporadic cases • DNA damage repair (MUTYH) Chromatin remodeling (MEN1) • Telomere maintenance (MEN1, DAXX, ATRX) mTOR signaling – Hereditary: 17% of patients with germline mutation Li X, Wang C, et al. Cancer Med 2018 Scarpa A, Grimond S, et al. NatureS L I2017 D E 2 Pathology Classification European American Joint World Health Organization Neuroendocrine Committee on Cancer (WHO) Tumor Society (AJCC) (ENETS) Grade Ki-67 Mitotic rt TNM TNM T1: limit to pancreas, <2 cm T1: limit to pancreas, ≦2 cm T2: limit to pancreas, 2-4 cm T2: >limit to pancreas, 2 cm T3: limit to pancreas, >4 cm, T3: beyond pancreas, no celiac or Low ≤2% <2 invades duodenum, bile duct SMA T4: beyond pancreas, invasion involvement adjacent organs or vessels T4: involves celiac or SMA N0: node negative No: node negative Intermed 3-20% 2-20 N1: node positive N1: node positive M0: no metastases M0: no metastases High >20% >20 M1: metastases M1: metastases S L I D E 3 Classification Based on Functionality • Nonfunctioning tumors – No clinical symptoms (can still produce hormone) – Accounts for 40% of tumors – 60-85%
    [Show full text]
  • Preclinical Cushing's Syndrome Resulting from Adrenal Black
    Endocrine Journal 2007, 54 (4), 543–551 Preclinical Cushing’s Syndrome Resulting from Adrenal Black Adenoma Diagnosed with Diabetic Ketoacidosis TOSHIO KAHARA, CHIKASHI SETO*, AKIO UCHIYAMA**, DAISUKE USUDA, HIROSHI AKAHORI, EIJI TAJIKA*, ATSUO MIWA**, RIKA USUDA, TAKASHI SUZUKI*** AND HIRONOBU SASANO*** Department of Internal Medicine, Toyama Prefectural Central Hospital, 2-2-78 Nishinagae, Toyama 930-8550, Japan *Department of Urology, Toyama Prefectural Central Hospital, 2-2-78 Nishinagae, Toyama 930-8550, Japan **Department of Pathology, Toyama Prefectural Central Hospital, 2-2-78 Nishinagae, Toyama 930-8550, Japan ***Department of Pathology, Tohoku University School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan Abstract. A right adrenal tumor was incidentally discovered on abdominal computed tomography performed on a 53- year-old Japanese man, who had been hospitalized with diabetic ketoacidosis. Normal values were obtained for adrenal hormones in the morning after an overnight fast and urinary cortisol excretion after treatment of diabetic ketoacidosis with insulin. However, overnight dexamethasone administration with 1 mg or 8 mg did not completely suppress serum cortisol levels. There were no remarkable physical findings related to Cushing’s syndrome. The patient was diagnosed as having preclinical Cushing’s syndrome (PCS). Histological examination of the adrenalectomy specimen demonstrated adrenal black adenoma. Blood glucose levels subsequently improved after adrenalectomy, and the patient never developed adrenal insufficiency after hydrocortisone withdrawal. The patient was treated with diet therapy alone, and maintained good glycemic control. However, the patient still showed a diabetic pattern in an oral glucose tolerance test. It seems that the existence of PCS in addition to the underlying type 2 diabetes mellitus contributed to aggravation of blood glucose levels.
    [Show full text]
  • The Glucagonoma Syndrome And
    European Journal of Endocrinology (2004) 151 531–537 ISSN 0804-4643 REVIEW The glucagonoma syndrome and necrolytic migratory erythema: a clinical review Andre´ P van Beek, Ellen R M de Haas1, Willem A van Vloten2, Cees J M Lips3, Janine F M Roijers3 and Marijke R Canninga-van Dijk4 University Medical Center Groningen, Department of Endocrinology, PO Box 30.001, 9700 RB, Groningen, 1Erasmus MC - University Medical Center Rotterdam, Department of Dermatology, PO Box 1738, 3000 DR, Rotterdam, and Departments of 2Dermatology, 3Endocrinology and 4Pathology, University Medical Center Utrecht, PO Box 85.500, 3508 GA, Utrecht, The Netherlands (Correspondence should be addressed to A P van Beek; Email: [email protected]) Abstract The glucagonoma syndrome is a rare disease in which a typical skin disorder, necrolytic migratory erythema, is often one of the first presenting symptoms. Weight loss and diabetes mellitus are two other prevalent characteristics of this syndrome. Necrolytic migratory erythema belongs to the recently recognized family of deficiency dermatoses of which zinc deficiency, necrolytic acral erythema and pellagra are also members. It is typically characterized on skin biopsies by necrolysis of the upper epidermis with vacuolated keratinocytes. In persistent hyperglucagonemia, excessive stimulation of basic metabolic pathways results in diabetes mellitus at the expense of tissue glycogen stores, and muscle and fat mass. Multiple (essential) nutrient and vitamin B deficiencies develop, which contrib- ute to the dermatosis. In addition, glucagonomas may produce various other products, like pancreatic polypeptide, that add to the catabolic effects of glucagon. European Journal of Endocrinology 151 531–537 Introduction an appendectomy and at age 50 he was operated on because of bilateral inguinal herniae.
    [Show full text]